Campbell McInnes, Ph.D.

Associate Professor, Medicinal Chemistry

Office (803) 576-5684 | Cell (803) 338-6340

Coker Life Sciences 717A | Laboratory, CLS717, 718

mcinnes@sccp.sc.edu

Research Interest

Current research is directed towards the discovery of small molecule protein kinase inhibitors targeting signaling and cell cycle proteins involved in tumor proliferation. Rather than blocking ATP binding, we are focused on the development of very selective inhibitors by targeting protein-protein interactions involved in allosteric regulation of kinase activity and other non-catalytic functions of such enzymes.

The McInnes laboratory have developed the REPLACE strategy in order to more effectively target PPI’s in general and have validated this approach with several kinase targets. Promising compounds obtained through application of REPLACE are being developed further by medicinal chemistry, cellular phenotypic characterization and testing in preclinical tumor models. Dr. McInnes has recently started a spin-off company called PPI Pharmaceuticals, LLC in order to exploit promising compounds discovered in his academic laboratory. 

Research Highlight

Education

Bachelor of Science
Chemistry, 1986

University of Guelph, Canada

Doctor of Philosophy
Chemistry, 1991

University of Edinburgh, UK

Postdoctoral
Biochemistry, 1999

University of Alberta, Canada

 

Research Support

NIH R41 CA189620

 

Biography

Dr. McInnes has worked for 20+ years in the fields of synthetic organic chemistry, structural biology and computational chemistry towards the discovery and development of anti-cancer therapeutics in both academia and industry. Prior to joining USC, he was head of the structure-guided medicinal chemistry group at Cyclacel Inc in the United Kingdom., a company started by Prof. Sir David Lane, co-discoverer of the p53 protein.  

  • Nandha Padmavathy, P., Craig, S., Liu, S., Anderson, E., Grigoroudis, AΙ., Kontopidis, G,  and McInnes, C., Iterative conversion of peptidic cyclin groove inhibitors into drug-like CDK inhibitors with anti-tumor activity, J. Med. Chem. (2015) 58(1):433-42. PMID: 25454794
  • Craig, SN, Wyatt, MD, McInnes, C. Current assessment of polo-like kinases as anti-tumor drug targets. Expert Opin. Drug Discov. (2014) 9(7):773-89. PMID: 24819909
  • Premnath, P.N., Liu, S., Perkins, T., Anderson, E and McInnes, C. Fragment based discovery of arginine isosteres through REPLACE: towards non-ATP competitive CDK inhibitors. Bioorg. Med. Chem (2014), 22(1):616-22  PMID: 24286762
  • Liu, S., Premnath, P.N., Bolger, J., Kirkland, L., Perkins, T., Kontopidis G, andMcInnes, C. Optimization of CDK/cyclin groove inhibitors through REPLACE mediated fragment assembly. Journal of Medicinal Chemistry, 2013, 56 (4), pp 1573–1582 PMID: 23323521
  • McInnes, C*, Estes, K, Baxter, M. Zhang, Z,  Doaa Boshra Farag, Paul Johnson, John Lazo, and Michael D. Wyatt  Targeting sub-cellular localization through the Polo-Box Domain: non-ATP competitive Inhibitors recapitulate a PLK1 phenotype. Molecular Cancer Therapeutics, 2012, August: 11(8): 1683-1692 (Featured on the cover). PMID: 22848093

More Selected publications

  • Liu, S., Premnath, P.N., Bolger, J., Kirkland, L., Perkins, T., Kontopidis G, and McInnes, C. Optimization of CDK/cyclin groove inhibitors through REPLACE mediated fragment assembly. Journal of Medicinal Chemistry, 2013, 56 (4), pp 1573–1582 PMID: 23323521
  • McInnes, C*, Estes, K, Baxter, M. Zhang, Z,  Doaa Boshra Farag, Paul Johnson, John Lazo, and Michael D. Wyatt  Targeting sub-cellular localization through the Polo-Box Domain: non-ATP competitive Inhibitors recapitulate a PLK1 phenotype. Molecular Cancer Therapeutics, 2012, August: 11(8): 1683-1692 (Featured on the cover). PMID: 22848093
  • Liu S, Bolger JK, Kirkland LO, Premnath PN, McInnes C. Structural and Functional Analysis of Cyclin D1 Reveals   p27 and Substrate Inhibitor Binding Requirements. ACS Chemical Biology. 2010 Dec 17;5(12):1169-82. PMID: 20843055
  • McIntyre NA, McInnes C (joint first author), Griffiths G, Barnett AL, Kontopidis G, Slawin AM, Jackson W, Thomas M, Zheleva DI, Wang S, Blake DG, Westwood NJ, Fischer PM. Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. J Med Chem. 2010 Mar 11;53(5):2136-45. PMID: 20146435
  • Kontopidis, G, Andrews MA, McInnes C (joint first author), Plater, A, Innes L, Renachowski, S, Cowan A and Fischer PM.  Truncation and Optimization of Peptide Inhibitors of Cyclin-Dependent Kinase 2-Cyclin A Through Structure- Guided Design ChemMedChem 2009, 4, 1120. PMID: 19472269
  •  Andrews MJ, Kontopidis G, McInnes C (joint first author), Plater A, Innes L, Cowan A, Jewsbury P, Fischer PM. REPLACE: A Strategy for Iterative Design of Cyclin Groove Inhibitors Chembiochem. 2006, 7(12): 1909. PMID: 17051658
  • McInnes C, Mazumdar C, Mezna M, Meades C, Midgley C, Scaerou F, Carpenter C, Mackenzie M, Taylor P, Walkinshaw M, Fischer P and Glover D. Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance. 2006 Nature Chemical Biology 2(11):608-17. PMID: 17028581